Recapitulating and Deciphering Tumor-stroma Microenvironment by Using a “LEGO” like 3D printed microfluidic device

The tumor-stroma microenvironment is extremely important on tumor progression, metastasis and angiogenesis. Development of in vitro technology that can quantitatively gain migration and cell-cell interaction data is there high desirable. Conventional methods for study tumor migration and cell-cell interaction are plagued by inaccessible to get quantitative data or complication of microfabrication process which brings into additional efforts rather than study the biological question itself. Herein, we developed a “LEGO”-like 3D printed device combined with a quantitative data gaining process which can be used for investigation into tumor cell migration process dynamically at single cell resolution and tumor-stromal interactions with high flexibility. These interactions showed to alter the genotype and phenotype of tumor cells or fibroblasts. RNA sequence analysis of homocultured and cocultured fibroblasts or HT1080 cells identified several differentially expressed genes. We found that fibroblasts cocultured with HT1080 for 24 h were in an intermediate state relative to the CAF and the normal fibroblast, and promoted tumor cell migration but inhibited tumor cell proliferation. In terms of DEGs from fibroblasts and HT1080 cells, we deciphered this phenomenon in detail. Whole mRNA profiles of HT1080 (Coculture with NHDF vs Homoculture) and NHDF (Coculture with HT1080 vs Homoculture) were generated by deep sequencing, in triplicate, using Illumina HiSeq